Peripheral Pain Captured Centrally: Altered Brain Morphology on MRI in Small Fiber Neuropathy Patients With and Without an SCN9A Gene Variant.

The current study aims to characterize brain morphology of pain as reported by small fiber neuropathy (SFN) patients with or without a gain-of-function variant involving the SCN9A gene and compare these with findings in healthy controls without pain. The Neuropathic Pain Scale was used in patients with idiopathic SFN (N = 20) and SCN9A-associated SFN (N = 12) to capture pain phenotype. T1-weighted, structural magnetic resonance imaging (MRI) data were collected in patients and healthy controls (N = 21) to 1) compare cortical thickness and subcortical volumes and 2) quantify the association between severity, quality, and duration of pain with morphological properties. SCN9A-associated SFN patients showed significant (P < .017, Bonferroni corrected) higher cortical thickness in sensorimotor regions, compared to idiopathic SFN patients, while lower cortical thickness was found in more functionally diverse regions (eg, posterior cingulate cortex). SFN patient groups combined demonstrated a significant (Spearman's ρ = .44-.55, P = .005-.049) correlation among itch sensations (Neuropathic Pain Scale-7) and thickness of the left precentral gyrus, and midcingulate cortices. Significant associations were found between thalamic volumes and duration of pain (left: ρ = -.37, P = .043; right: ρ = -.40, P = .025). No associations were found between morphological properties and other pain qualities. In conclusion, in SCN9A-associated SFN, profound morphological alterations anchored within the pain matrix are present. The association between itch sensations of pain and sensorimotor and midcingulate structures provides a novel basis for further examining neurobiological underpinnings of itch in SFN. PERSPECTIVE: Cortical thickness and subcortical volume alterations in SFN patients were found in pain hubs, more profound in SCN9A-associated neuropathy, and correlated with itch and durations of pain. These findings contribute to our understanding of the pathophysiological pathways underlying chronic neuropathic pain and symptoms of itch in SFN.

Identification and characterization of a novel recessive KCNQ1 mutation associated with Romano-Ward Long-QT syndrome in two Iranian families.

BACKGROUND: One of the foremost causes of sudden cardiac death in the young is an inherent cardiac arrhythmia known as Long-QT syndrome (LQTS). Whereas heterozygous mutations typically lead to the Romano-Ward type of LQTS, We have provided a further evidence for the recessive transmission of a novel KCNQ1 gene mutation in two consanguineous families for the first time in Iran. METHODS: Next generation sequencing, DNA Sanger sequencing and haplotype analysis were performed for genotype determination. Twelve different in silico tools were used for predicting the variant pathogenecity along with the family and population study. RESULTS: A novel recessive KCNQ1 variant (p.D564G) was revealed in none of the unrelated healthy individuals but four patients in two apparently unrelated families. The variant was classified as a likely pathogenic mutation by combining the resulted criteria for the changed amino acid. CONCLUSIONS: Identification of the novel mutation not only supports the genetic testing as a definitive diagnostic tool for detection of at risk family members, but also emphasizes its screening in Iranian LQTS patients as this mutation is very likely a founder mutation in Iran.